Evaluation of Loco-Regional Skin Toxicity Induced by an In Situ Forming Depot after a Single Subcutaneous Injection at Different Volumes and Flow Rates in Göttingen Minipigs
| Autor: | Adolfo López-Noriega, Anne-Pascale Trichet, Jacques Descotes, Charlotte Peloso, Christophe Roberge, Joël Richard |
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| Rok vydání: | 2021 |
| Předmět: |
In situ
medicine.medical_specialty QH301-705.5 Swine Depot Injections Subcutaneous subcutaneous injection Article Catalysis Inorganic Chemistry Subcutaneous injection Animal model Animals Medicine Biology (General) Physical and Theoretical Chemistry QD1-999 Molecular Biology Spectroscopy Skin Ultrasonography business.industry Drug Administration Routes Organic Chemistry Ultrasound General Medicine minipig Immunohistochemistry loco-regional skin tolerability Computer Science Applications Chemistry Skin toxicity Tolerability in situ forming depots sustained release drug delivery Swine Miniature Histopathology flow rate Nuclear medicine business |
| Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 22, Iss 9250, p 9250 (2021) Volume 22 Issue 17 |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms22179250 |
| Popis: | The present study aims to investigate the loco-regional tolerability and injection parameters (i.e., flow rate and administration volume) of an in situ forming depot (ISFD) in Göttingen minipigs, to secure both the therapeutic procedure and compliance in chronic medical prescriptions. The ISFD BEPO® technology (MedinCell S.A.) is investigated over 10 days, after a single subcutaneous injection of test item based on a DMSO solution of diblock and triblock polyethylene glycol-polylactic acid copolymers. Injection sites are systematically observed for macroscopic loco-regional skin reactions as well as ultrasound scanning, enabling longitudinal in vivo imaging of the depot. Observations are complemented by histopathological examinations at 72 h and 240 h post-injection. Overall, no treatment-emergent adverse effects are macroscopically or microscopically observed at the subcutaneous injection sites, for the tested injection flow rates of 1 and 8 mL/min and volumes of 0.2 and 1 mL. The histopathology examination confirms an expected foreign body reaction, with an intensity depending on the injected volume. The depot morphology is similar irrespective of the administration flow rates. These results indicate that the ISFD BEPO® technology can be considered safe when administered subcutaneously in Göttingen minipigs, a human-relevant animal model for subcutaneous administrations, in the tested ranges. |
| Databáze: | OpenAIRE |
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